The clinical gold standard in orthopaedics for treating fractures with large bone defects is still the use of autologous, cancellous bone autografts. While this material provides a strong healing response, the use of autografts is often associated with additional morbidity. Therefore, there is a demand for off-the-shelf biomaterials that perform similar to autografts. Biomechanical assessment of such a biomaterial in vivo has so far been limited. Recently, the development of high-resolution peripheral quantitative computed tomography (HR-pQCT) has made it possible to measure bone structure in humans in great detail. Finite element analysis (FEA) has been used to accurately estimate bone mechanical function from three-dimensional CT images. The aim of this study was therefore to determine the feasibility of these two methods in combination, to quantify bone healing in a clinical case with a fracture at the distal radius which was treated with a new bone graft substitute. Validation was sought through a conceptional ovine model. The bones were scanned using HR-pQCT and subsequently biomechanically tested. FEA-derived stiffness was validated relative to the experimental data. The developed processing methods were then adapted and applied to in vivo follow-up data of the patient. Our analyses indicated an 18% increase of bone stiffness within 2 months. To our knowledge, this was the first time that microstructural finite element analyses have been performed on bone-implant constructs in a clinical setting. From this clinical case study, we conclude that HR-pQCT-based micro-finite element analyses show high potential to quantify bone healing in patients. Copyright © 2010 John Wiley & Sons, Ltd.